Kanno Masafumi, Kano Satoshi, Imamura Yoshinori, Kawakita Daisuke, Narita Norihiko, Tada Yuichiro, Ito Yumi, Morikawa Taiyo, Imoto Yoshimasa, Kato Yukinori, Takabayashi Tetsuji, Fujieda Shigeharu
Division of Otorhinolaryngology-Head and Neck Surgery, Department of Sensory and Locomotor Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
Department of Otolaryngology-Head and Neck Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
Cancer Treat Rev. 2025 Jul 11;139:102993. doi: 10.1016/j.ctrv.2025.102993.
Salivary duct carcinoma (SDC) is a rare and highly aggressive malignancy of the salivary glands. For patients ineligible for curative surgery or definitive radiotherapy, treatment options remain limited owing to the absence of standardized therapeutic protocols. This review draws upon major salivary gland cancer guidelines and integrates molecular profiles with clinical response data to propose an evidence-based treatment algorithm that stratifies patients into four groups according to the expression status of human epidermal growth factor receptor 2 (HER2) and androgen receptor (AR). In HER2-positive tumors, HER2-targeted therapy constitutes the standard of care, with trastuzumab plus docetaxel providing clinical benefit. Antibody-drug conjugates, such as trastuzumab deruxtecan, have demonstrated efficacy even in patients with disease progression during trastuzumab-based therapy. In AR-positive tumors, androgen deprivation therapy, particularly combined androgen blockade, has demonstrated clinical activity, though concurrent molecular characteristics may influence treatment outcomes. In HER2-positive/AR-positive tumors, HER2-targeted therapy is generally prioritized, although the absence of validated predictive biomarkers and defined thresholds remains a clinical challenge. For HER2-negative and AR-negative tumors, or those refractory to either or both targeted approaches, cytotoxic chemotherapy remains a viable option. Immune checkpoint inhibitors may offer benefits in tumors with high PD-L1 expression, although data on their role in SDC remain limited. Next-generation sequencing is recommended to identify actionable alterations (e.g., NTRK, BRAF, FGFR, HRAS) that may guide targeted therapy or clinical trial enrollment. Integrating comprehensive molecular profiling into treatment decision-making is essential to optimizing outcomes in advanced SDC.
涎腺导管癌（SDC）是一种罕见且侵袭性很强的涎腺恶性肿瘤。对于不符合根治性手术或根治性放疗条件的患者，由于缺乏标准化的治疗方案，治疗选择仍然有限。本综述借鉴了主要的涎腺癌指南，并将分子特征与临床反应数据相结合，提出了一种基于证据的治疗算法，根据人表皮生长因子受体2（HER2）和雄激素受体（AR）的表达状态将患者分为四组。在HER2阳性肿瘤中，HER2靶向治疗是标准治疗方法，曲妥珠单抗联合多西他赛可带来临床获益。抗体药物偶联物，如曲妥珠单抗德鲁昔康，即使在基于曲妥珠单抗治疗期间疾病进展的患者中也显示出疗效。在AR阳性肿瘤中，雄激素剥夺治疗，尤其是联合雄激素阻断，已显示出临床活性，尽管同时存在的分子特征可能会影响治疗结果。在HER2阳性/AR阳性肿瘤中，通常优先进行HER2靶向治疗，尽管缺乏经过验证的预测生物标志物和明确的阈值仍然是一个临床挑战。对于HER2阴性和AR阴性肿瘤，或对任何一种或两种靶向治疗方法均耐药的肿瘤，细胞毒性化疗仍然是一种可行的选择。免疫检查点抑制剂可能对PD-L1高表达的肿瘤有益，尽管其在SDC中的作用数据仍然有限。建议进行二代测序以识别可能指导靶向治疗或临床试验入组的可操作改变（例如，NTRK、BRAF、FGFR、HRAS）。将全面的分子特征纳入治疗决策对于优化晚期SDC的治疗结果至关重要。
